Journal
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
Volume 103, Issue -, Pages 791-801Publisher
ELSEVIER
DOI: 10.1016/j.ijbiomac.2017.05.125
Keywords
Docetaxel; Quality by design; Box-Behnken design; Design of experiment; Cytotoxicity
Funding
- UGC, New Delhi, India
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Long-circulating nanoparticles (NPs) are promising drug delivery vehicles which target solid tumors via enhanced permeation and retention effect. Plackett-Burman (PBD) and Box-Behnken (BBD) designs were adopted to study the effects of factors viz. polymer concentration, surfactant concentration, homogenizer speed, homogenization time and ultrasonication time on responses. A graphical and numerical optimization technique was used to obtain predicted value of the response. The drug entrapment efficiency was approximately 39 +/- 0.85%. The particle size of the nanoparticles was found to be 260 +/- 2.85 nm, while the zeta potential was-18 +/- 2.12 mV, indicating more stable particles. SEM, TEM, and AFM were used for characterization of surface morphology and the physicochemical characters of NPs. A pharmacokinetic evaluation carried out intravenous administration in healthy Charles Foster rats displayed enhanced systemic bioavailability and plasma drug concentration. The in vivo-in silico assessment by GastroPlus (TM) showed good prediction accuracy and presented best-fit model. Nanoparticles were also studied for stability testing and were found to be stable concerning their drug content and physical characters. In vitro cytotoxicity was assessed using MCF-7 for percentage inhibition of human breast cancer cell line. Anti-cancer studies of optimized NPs showed a significant increase in efficacy as observed by relative tumor volume up to 30 days. (C) 2017 Elsevier B.V. All rights reserved.
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